The theme of the Program Project entitled 'Anatomic, physiologic and Cognitive Pathology of AD' is the elucidation of the pathophysiology of AD as a function of disease progression. This theme will be approached all the way from behavioral and in vivo anatomical perspectives (i.e., structural and functional imaging) to cell and molecular biological levels. The program brings together a number of basic scientists and clinicians from two major Chicago-area medical schools, namely Rush- Presbyterian-St. Luke's Medical Center and Northwestern University Medical Center. Colleagues from Ohio State University, Stanford University and the University of Miami are also participating. The project will be based at the Rush-Presbyterian-St. Luke's Medical Center. The proposed Program Project consists of administrative, clinical, neuropathology and statistics and data management cores, in addition to the following six research projects: 1) In vivo Detection of the Anatomic and Functional Progression of AD (Leyla del Toledo-Morrell, Project Leader); 2) fMRI Analysis of Medical Temporal Lobe Function in Aging and AD (John Gabrieli and Glenn Stebbins, Project Leaders); 3) Dopaminergic Mesocortical System's in MCI and AD (Jeffrey Kordower, Project Leader); 5) Tau Truncation and Conformation in AD Progression (Lester Binder, Project Leader); and 6) Protein Kinase Markers of AD Progression (Jeff Kuret, Project Leader). Each core will support at least three of these research projects. A major strength of the proposed research is that all of the projects will use well characterized participants (or brain tissue from participants) who will be followed clinically with yearly evaluations.